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J Hematol Oncol. 2018 Sep 3;11(1):111. doi: 10.1186/s13045-018-0654-9.

Histone deacetylase 6 in cancer.

Li T1,2, Zhang C1,2, Hassan S1,2,3, Liu X1,2, Song F4, Chen K4, Zhang W5, Yang J6,7.

Author information

1
Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China.
2
National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China.
3
International Medical School, Tianjin Medical University, Tianjin, 300061, People's Republic of China.
4
Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China.
5
Cancer Genomics and Precision Medicine, Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, USA.
6
Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China. yangjilong@tjmuch.com.
7
National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China. yangjilong@tjmuch.com.

Abstract

Histone acetylation and deacetylation are important epigenetic mechanisms that regulate gene expression and transcription. Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family that not only participates in histone acetylation and deacetylation but also targets several nonhistone substrates, such as α-tubulin, cortactin, and heat shock protein 90 (HSP90), to regulate cell proliferation, metastasis, invasion, and mitosis in tumors. Furthermore, HDAC6 also upregulates several critical factors in the immune system, such as program death receptor-1 (PD-1) and program death receptor ligand-1 (PD-L1) receptor, which are the main targets for cancer immunotherapy. Several selective HDAC6 inhibitors are currently in clinical trials for cancer treatment and bring hope for patients with malignant tumors. A fuller understanding of HDAC6 as a critical regulator of many cellular pathways will help further the development of targeted anti-HDAC6 therapies. Here, we review the unique features of HDAC6 and its role in cancer, which make HDAC6 an appealing drug target.

KEYWORDS:

Cortactin; HDAC6; HSP90; PD-1/PD-L1; Target therapy; α-tubulin

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